For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently described, MUC1. Affected family members show renal fibrosis in the biopsy and gradually declining renal function, with renal failure usually occurring between the third and sixth decade of life. Here we describe 10 families and define eligibility criteria to consider this type of inherited disease, as well as propose a practicable approach for diagnosis. In contrast to what the frequently used term 'Medullary Cystic Kidney Disease' implies, development of (medullary) cysts is neither an early nor a typical feature, as determined by MRI. In addition to Sanger and gene panel sequencing of the four genes, we established SNaPshot minisequencing for the predescribed cytosine duplication within a distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of 9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On the basis of clinical and pathological characteristics we propose the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' as an improved terminology. This should enhance recognition and correct diagnosis of affected individuals, facilitate genetic counseling, and stimulate research into the underlying pathophysiology.

Prevalence of ADPKD is overestimated by 2- to 5-fold and close to the limit of RDs which may be of broad clinical, logistic and policy implications.

The changes of aroma ingredients during the process of flower opening from Bulgarian rose were monitored by head space method and solvent extraction.W e also analyzed contents of glycosidic alcoholic aroma together with activities of the hydrolytic enzymes throughout the flower development and the opening. At flower petal opening time, the total amount of aromas in the head space gas reached the highest level. The concentration of citronellol was abundant in the head space gas at this stage, whereas the concentration o f 2-phenylethanol became higher than that of citronellol 4 hr after the opening stage. In the volatile extracts, higher accumulation was observed in 2-phenylethanol than those of monoterpenoids at this stage, and the content of the former still increased after flower opening. Glycosidic citronellol, geraniol, and other m onoterpenes started their accumulation ju st before flower opening stage and then reached the maximum level. The amount of these glycosidic compounds were less than those in the volatile extracts. In contrast to the monoterpenes, 2-phenylethyl glycosides accumulated in a higher level than in the volatile extracts starting at least 12 hr before the opening stage. The amount of the glycosidic precursors of 2-phenylethanol detected in the rose petals before flower opening always was higher than the amount of 2-phenylethanol which was released later. The decline of glycosidic 2-phenylethanol at flower opening stage may be due to partial enzymatic hydrol­ysis. Thereafter a drastic decline was observed, indicating that rapid enzymatic hydrolysis occurred during these stages.

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The nuclear bile acid receptor Farnesoid X receptor (FXR) is strongly expressed in liver and intestine, controls bile acid and lipid homeostasis and exerts tumor-protective functions in liver and intestine. Histidine-rich glycoprotein (HRG) is an abundant plasma protein produced by the liver with the proposed function as a pattern recognition molecule involved in the clearance of immune complexes, necrotic cells and pathogens, the modulation of angiogenesis, the normalization of deranged endothelial vessel structure in tumors and tumor suppression. FXR recognition sequences were identified within a human HRG promoter fragment that mediated FXR/FXR-agonist dependent reporter gene activity in vitro. We show that HRG is a novel transcriptional target gene of FXR in human hepatoma cells, human upcyteV R primary hepatocytes and 3D human liver microtissues in vitro and in mouse liver in vivo. Prolonged administration of the potent nonsteroidal FXR agonist PX20606 increases HRG levels in mouse plasma. Finally, daily oral administration of this FXR agonist for seven days resulted in a significant increase of HRG levels in the plasma of healthy human male volunteers during a clinical Phase I safety study. HRG might serve as a surrogate marker indicative of liver-specific FXR activation in future human clinical studies. Furthermore, potent FXR agonists might be beneficial in serious health conditions where HRG is reduced, for example, in hepatocellular carcinoma but also other solid cancers, liver failure, sepsis and pre-eclampsia.